Solution and calorimetric thermodynamic study of a new 1 : 1 sulfamethazine-3-methylsalicylic acid co-crystal

Dipali Ahuja, Michael Svärd, Matteo Lusi, Åke C. Rasmuson

Research output: Contribution to journalArticlepeer-review

Abstract

A new 1 : 1 co-crystal of sulfamethazine (API, SMT) and 3-methylsalicylic acid (coformer, 3mSA) has been synthesized and its crystal structure solved by single crystal X-ray diffraction (XRD). The co-crystal has been thoroughly characterized by powder XRD, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The pure co-crystal could be synthesized by solvent drop grinding, cooling crystallization and slurry conversion co-crystallization. Ternary phase diagrams have been constructed in methanol and acetonitrile at 30 °C. The co-crystal exhibits incongruent dissolution in both solvents. The thermodynamics of co-crystal formation have been estimated from solubility data and calorimetric data, respectively, showing that formation of the SMT-3mSA co-crystal from its solid components is spontaneous and entropy-driven. The co-crystal formation is associated with a 5% increase in molecular volume. A relationship between the size of the region where the co-crystal is the most stable solid phase and the relative solubility of the co-crystal components has been uncovered. The co-crystal region becomes smaller as the solubility ratio increases.

Original languageEnglish
Pages (from-to)3463-3473
Number of pages11
JournalCrystEngComm
Volume22
Issue number20
DOIs
Publication statusPublished - 28 May 2020

Fingerprint

Dive into the research topics of 'Solution and calorimetric thermodynamic study of a new 1 : 1 sulfamethazine-3-methylsalicylic acid co-crystal'. Together they form a unique fingerprint.

Cite this